Decoding Diffuse Midline Gliomas: A Comprehensive Review of Pathogenesis, Diagnosis and Treatment

Simple Summary Diffuse midline glioma (DMG) is a highly aggressive brain tumor primarily affecting children and young adults. It grows diffusely in midline structures. Unfortunately, DMG has a very poor prognosis, rendering traditional treatment such as radiation therapy and chemotherapy limited in controlling tumor growth. Ongoing research aims to understand the tumor's biology and develop new therapies. Genomic profiling has identified specific mutations, such as H3F3A and HIST1H3B gene alterations, which may offer potential targets for future treatment. However, managing DMGs remains challenging, and more effective therapies are desperately needed to improve outcomes in affected individuals.Abstract Diffuse midline gliomas (DMGs) are a group of aggressive CNS tumors, primarily affecting children and young adults, which have historically been associated with dismal outcomes. As the name implies, they arise in midline structures in the CNS, primarily in the thalamus, brainstem, and spinal cord. In more recent years, significant advances have been made in our understanding of DMGs, including molecular features, with the identification of potential therapeutic targets. We aim to provide an overview of the most recent updates in the field of DMGs, including classification, molecular subtypes, diagnostic techniques, and emerging therapeutic strategies including a review of the ongoing clinical trials, thus providing the treating multidisciplinary team with a comprehensive understanding of the current landscape and potential therapeutic strategies for this devastating group of tumors.